Department of Psychiatry, University of New Mexico, Albuquerque, NM 87131-0001, USA.
Mol Psychiatry. 2010 Jun;15(6):629-36. doi: 10.1038/mp.2009.121. Epub 2009 Nov 17.
We investigated glutamate-related neuronal dysfunction in the anterior cingulate (AC) early in schizophrenia before and after antipsychotic treatment. A total of 14 minimally treated schizophrenia patients and 10 healthy subjects were studied with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the AC, frontal white matter and thalamus at 4 T. Concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln) and Gln/Glu ratios were determined and corrected for the partial tissue volume. Patients were treated with antipsychotic medication following a specific algorithm and (1)H-MRS was repeated after 1, 6 and 12 months. There were group x region interactions for baseline NAA (P=0.074) and Gln/Glu (P=0.028): schizophrenia subjects had lower NAA (P=0.045) and higher Gln/Glu (P=0.006) in the AC before treatment. In addition, AC Gln/Glu was inversely related to AC NAA in the schizophrenia (P=0.0009) but not in the control group (P=0.92). Following antipsychotic treatment, there were no further changes in NAA, Gln/Glu or any of the other metabolites in any of the regions studied. We conclude that early in the illness, schizophrenia patients already show abnormalities in glutamatergic metabolism and reductions in NAA consistent with glutamate-related excitotoxicity.
我们研究了精神分裂症早期前扣带回(AC)中与谷氨酸相关的神经元功能障碍,在使用抗精神病药物治疗前后进行了研究。共有 14 名未经治疗的精神分裂症患者和 10 名健康受试者在 4T 下进行了单体质子磁共振波谱(1H-MRS)的 AC、额叶白质和丘脑。测定了 N-乙酰天冬氨酸(NAA)、谷氨酸(Glu)、谷氨酰胺(Gln)和 Gln/Glu 比值,并对部分组织体积进行了校正。患者根据特定的算法接受抗精神病药物治疗,并在 1、6 和 12 个月后重复 1H-MRS。基线 NAA(P=0.074)和 Gln/Glu(P=0.028)存在组 x 区域交互作用:在治疗前,精神分裂症患者的 NAA(P=0.045)和 Gln/Glu(P=0.006)较低。此外,AC 的 Gln/Glu 与 AC 的 NAA 呈负相关在精神分裂症患者中(P=0.0009),而在对照组中则无相关性(P=0.92)。在抗精神病药物治疗后,在研究的任何区域中,NAA、Gln/Glu 或任何其他代谢物均未发生进一步变化。我们得出结论,在疾病早期,精神分裂症患者已经表现出谷氨酸能代谢异常和 NAA 减少,这与谷氨酸相关的兴奋性毒性一致。